Expert Opinion on Therapeutic Targets最新文献_第2页

Hepcidin as a therapeutic target in iron overload. 作为铁超载治疗靶点的肝素

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-12-01 Epub Date: 2024-12-18 DOI: 10.1080/14728222.2024.2443081

Miriam Sandnes, Håkon Reikvam

{"title":"Hepcidin as a therapeutic target in iron overload.","authors":"Miriam Sandnes, Håkon Reikvam","doi":"10.1080/14728222.2024.2443081","DOIUrl":"10.1080/14728222.2024.2443081","url":null,"abstract":"Introduction: Dysregulation of the hepcidin-ferroportin axis is a hallmark in the pathogenesis of iron overload, ultimately leading to end-organ injury. Hereditary hemochromatosis and iron-loading anemias are characterized by a hepcidin deficiency, making hepcidin a novel therapeutic target for preventing and managing iron overload.Areas covered: Modulators of hepcidin expression and molecules mimicking hepcidin are emerging as highly promising therapeutic strategies. We present a summary of results from preclinical and clinical trials of such therapies in models of iron overload.Expert opinion: Current treatment alternatives in iron overload fail to address the underlying hepcidin deficiency - and may even exacerbate it. Until hepcidin-targeting therapies become available, several challenges remain, including the need to optimize dosing in order to manage the narrow treatment window and improving specificity in targeting iron metabolism pathways exclusively. Long-term studies are crucial to fully assess both the benefits and risks of these therapies and to explore their potential utility in combination with existing treatment guidelines. Furthermore, these therapies are expected to have applications, particularly in addressing other iron-maldistributed disorders, as seen in anemia of chronic disease and inflammation.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1039-1046"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unlocking the potential of melanotransferrin (CD228): implications for targeted drug development and novel therapeutic avenues. 释放黑色素转铁蛋白（CD228）的潜力：对靶向药物开发和新治疗途径的影响

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-12-01 Epub Date: 2024-12-19 DOI: 10.1080/14728222.2024.2441705

Yanan Zhang, Deyong Song, Xiaolei Han, Hong Liu, Yunfan Wang, Xianju Wang, Changlin Dou

{"title":"Unlocking the potential of melanotransferrin (CD228): implications for targeted drug development and novel therapeutic avenues.","authors":"Yanan Zhang, Deyong Song, Xiaolei Han, Hong Liu, Yunfan Wang, Xianju Wang, Changlin Dou","doi":"10.1080/14728222.2024.2441705","DOIUrl":"10.1080/14728222.2024.2441705","url":null,"abstract":"Introduction: Melanotransferrin (CD228), a cell membrane-anchored protein, has emerged as a significant cancer antigen due to its high expression in various solid tumors. This review synthesizes the current understanding and therapeutic potential of CD228.Areas covered: We conducted a literature search using PubMed, Web of Science, and ClinicalTrials.gov with the keywords 'melanotransferrin' and 'CD228.' Our comprehensive review examines CD228 and its isoforms, membrane-bound CD228 (mMFI2) and soluble CD228 (sMFI2), their roles in tumorigenesis, angiogenesis, endothelial cell migration, plasminogen activation, and transendothelial transport across the BBB, as well as the current state of drug development efforts targeting CD228.Expert opinion: Targeting CD228 represents a promising therapeutic strategy in oncology, with mMFI2 as a potential target for solid tumors and sMFI2 valuable for disease diagnosis in malignant tumors, Alzheimer's disease, and arthritis, and facilitating macromolecular drug delivery across the blood-brain barrier (BBB). Despite its potential to transform the treatment landscape for numerous solid cancers, further research into the precise mechanisms and clinical translation of CD228-directed treatments is needed to maximize its therapeutic utility.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1117-1129"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunotherapies in breast cancer: harnessing the cancer immunity cycle. 乳腺癌的免疫疗法：利用癌症免疫循环。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-11-10 DOI: 10.1080/14728222.2024.2427038

Vincent Lok, Sy Olson-McPeek, Grace Spiegelhoff, Jaqueline Cortez, David Detz, Brian Czerniecki

引用次数: 0

Targeted therapeutic strategies for the kidney. 肾脏靶向治疗策略。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-11-03 DOI: 10.1080/14728222.2024.2421756

Fei Yuan, Lilach O Lerman

{"title":"Targeted therapeutic strategies for the kidney.","authors":"Fei Yuan, Lilach O Lerman","doi":"10.1080/14728222.2024.2421756","DOIUrl":"10.1080/14728222.2024.2421756","url":null,"abstract":"Introduction: Kidney diseases impose a significant burden with high incidence and mortality rates. Current treatment options for kidney diseases are limited, necessitating urgent development of novel and effective therapeutic strategies to delay or reverse disease progression. Targeted therapies for the kidney hold promise in significantly enhancing treatment outcomes, offering hope to patients afflicted with renal disorders.Areas covered: This review summarized advances in kidney-targeted therapies including genes, peptides and proteins, cell-based, nanoparticles, and localized delivery routes. We also explored the potential clinical applications, prospects, and challenges of targeted therapies for renal disorders.Expert opinion: Advances in targeted therapies for renal conditions have enhanced therapeutic outcomes. Clinical application of kidney-targeted therapies is currently limited by renal structure and the scarcity of robust biomarkers. Bridging the gap from basic and pre-clinical research targeting the kidney to achieving clinical translation remains a formidable challenge.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"979-989"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemokine signaling in tumors: potential role of CXC chemokines and their receptors as glioblastoma therapeutic targets. 肿瘤中的趋化因子信号：CXC 趋化因子及其受体作为胶质母细胞瘤治疗靶点的潜在作用。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-11-24 DOI: 10.1080/14728222.2024.2433130

Alessandro Corsaro, Beatrice Tremonti, Adriana Bajetto, Federica Barbieri, Stefano Thellung, Tullio Florio

{"title":"Chemokine signaling in tumors: potential role of CXC chemokines and their receptors as glioblastoma therapeutic targets.","authors":"Alessandro Corsaro, Beatrice Tremonti, Adriana Bajetto, Federica Barbieri, Stefano Thellung, Tullio Florio","doi":"10.1080/14728222.2024.2433130","DOIUrl":"10.1080/14728222.2024.2433130","url":null,"abstract":"Introduction: Glioblastoma is the most aggressive brain tumor, typically associated with poor prognosis. Its treatment is challenging due to the peculiar glioblastoma cell biology and its microenvironment complexity. Specifically, a small fraction of glioma stem cells within the tumor mass drives tumor growth and invasiveness by hijacking brain resident and immune cells. This process also involves modification of extracellular matrix components, such as collagen and glycoproteins, where the secretion of soluble mediators, particularly CXC chemokines, plays a significant role.Areas covered: We analyze the critical role of chemokines in glioblastoma tumorigenesis, proliferation, angiogenesis, tumor progression, and brain parenchyma invasiveness. Recent evidence highlights how chemokines and their receptors impact glioblastoma biology and represent potential therapeutic targets. Several studies show that chemokines modulate glioblastoma development by acting on glioma stem cell proliferation and self-renewal, promoting vasculogenic mimicry, and altering the extracellular matrix to facilitate tumor invasiveness.Expert opinion: There is clear evidence supporting CXC receptors (such as CXCR1, 2, 3, 4, and ACKR3/CXCR7) and their signaling pathways as promising pharmacological targets. This in-depth review of chemokine roles in glioblastoma development provides a critical evaluation of the possible clinical translation of innovative compounds targeting these ligand/receptor systems, leading to improved therapeutic outcomes for glioblastoma patients.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"937-952"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential molecular targets for the pharmacologic management of non-traumatic osteonecrosis. 非创伤性骨坏死药物治疗的潜在分子靶点。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-10-29 DOI: 10.1080/14728222.2024.2421755

Edward Y Cheng, Alireza Mirzaei

{"title":"Potential molecular targets for the pharmacologic management of non-traumatic osteonecrosis.","authors":"Edward Y Cheng, Alireza Mirzaei","doi":"10.1080/14728222.2024.2421755","DOIUrl":"10.1080/14728222.2024.2421755","url":null,"abstract":"Introduction: Non-traumatic osteonecrosis is a debilitating condition marked by bone death, primarily due to reduced blood supply. Currently, no effective pharmacologic intervention is available to manage this condition effectively.Areas covered: Lipid metabolic disorders, chronic inflammation, vascular dysfunction, coagulopathy, and impaired bone homeostasis are suggested as the key pathogenic mechanisms involved in the development of non-traumatic osteonecrosis. Targeting any of these dysfunctions offers a potential avenue for pharmacologic intervention. However, the potential molecular targets for pharmacologic treatment of non-traumatic osteonecrosis remain underexplored. In this study, we reviewed available databases to compile a comprehensive set of pathogenic mechanisms and corresponding therapeutic targets for non-traumatic osteonecrosis.Expert opinion: Evidence suggests that a single pathogenic mechanism cannot fully explain the development of osteonecrosis, supporting the adoption of a multi-pathogenic theory. This theory implies that effective management of non-traumatic osteonecrosis requires targeting multiple pathogenic mechanisms simultaneously. Moreover, the same pathogenic mechanisms are unlikely to explain osteonecrosis development in patients with different etiologies. Consequently, a one-size-fits-all approach to medication is unlikely to be effective across all types of non-traumatic osteonecrosis. Future research should, therefore, focus on developing multi-target pharmacologic treatments tailored to the specific etiology of non-traumatic osteonecrosis.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"991-1000"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRPC3: how current mechanistic understanding provides a basis for therapeutic targeting. TRPC3：当前的机理认识如何为靶向治疗提供依据。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-11-18 DOI: 10.1080/14728222.2024.2430520

Klaus Groschner

{"title":"TRPC3: how current mechanistic understanding provides a basis for therapeutic targeting.","authors":"Klaus Groschner","doi":"10.1080/14728222.2024.2430520","DOIUrl":"10.1080/14728222.2024.2430520","url":null,"abstract":"Introduction: Intensive and detailed investigations of the molecular function and cellular role of mammalian transient receptor potential canonical (TRPC) channels started back in the early 90th of the past century. Initial TRPC research was fueled by high hopes to resolve fundamental questions of cellular Ca2+ signaling. To date, we have learned important lessons in TRPC channel biology and biophysics, while little progress has been made in terms of therapeutic concepts.Areas covered: This is a critical account of recent progress in building a solid mechanistic basis for therapeutic interventions utilizing TRPC3 as a target. I focus on hurdles and key issues to be resolved, thereby drafting a list of essential scientific 'to-dos' on the way toward drugging of TRPC3.Expert opinion: Recent advances in the molecular physiology of TRPC3 include unveiling its lipid sensing machinery and the channels´ ability to serve spatiotemporally diverse Ca2+ signaling in a cell type- and context-dependent manner. The ongoing development of technology for high-precision manipulation of the channel opens up a view on novel therapeutic strategies. It is now to unravel the complex role of TRPC3 in human physiopathology, to pinpoint the channels´ therapeutic relevance, and to further refine technologies for targeted interventions.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"953-961"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advantages and disadvantages of targeting senescent endothelial cells in cardiovascular and cerebrovascular diseases based on small extracellular vesicles. 利用细胞外小泡靶向治疗心脑血管疾病中的衰老内皮细胞的利弊。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1080/14728222.2024.2421760

Wen Ma, Tingyuan Zhou, Songling Tang, Lu Gan, Yu Cao

{"title":"Advantages and disadvantages of targeting senescent endothelial cells in cardiovascular and cerebrovascular diseases based on small extracellular vesicles.","authors":"Wen Ma, Tingyuan Zhou, Songling Tang, Lu Gan, Yu Cao","doi":"10.1080/14728222.2024.2421760","DOIUrl":"10.1080/14728222.2024.2421760","url":null,"abstract":"Introduction: With the growth of the aging population, age-related diseases have become a heavy global burden, particularly cardiovascular and cerebrovascular diseases (CVDs). Endothelial cell (EC) senescence constitutes an essential factor in the development of CVDs, prompting increased focus on strategies to alleviate or reverse EC senescence.Areas covered: Small extracellular vesicles (sEVs) are cell-derived membrane structures, that contain proteins, lipids, RNAs, metabolites, growth factors and cytokines. They are widely used in treating CVDs, and show remarkable therapeutic potential in alleviating age-related CVDs by inhibiting or reversing EC senescence. However, unclear anti-senescence mechanism poses challenges for clinical application of sEVs, and a systematic review is lacking.Expert opinion: Targeting senescent ECs with sEVs in age-related CVDs treatment represents a promising therapeutic strategy, with modifying sEVs and their contents emerging as a prevalent approach. Nevertheless, challenges remain, such as identifying and selectively targeting senescent cells, understanding the consequences of removing senescent ECs and senescence-associated secretory phenotype (SASP), and assessing the side effects of therapeutic sEVs on CVDs. More substantial experimental and clinical data are needed to advance clinical practice.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1001-1015"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting mucosal healing in Crohn's disease: efficacy of novel pathways and therapeutic targets. 克罗恩病的靶向粘膜愈合：新途径和治疗靶点的疗效。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-11-29 DOI: 10.1080/14728222.2024.2433124

Lucia Centanni, Sarah Bencardino, Ferdinando D'Amico, Alessandra Zilli, Tommaso Lorenzo Parigi, Mariangela Allocca, Silvio Danese, Federica Furfaro

{"title":"Targeting mucosal healing in Crohn's disease: efficacy of novel pathways and therapeutic targets.","authors":"Lucia Centanni, Sarah Bencardino, Ferdinando D'Amico, Alessandra Zilli, Tommaso Lorenzo Parigi, Mariangela Allocca, Silvio Danese, Federica Furfaro","doi":"10.1080/14728222.2024.2433124","DOIUrl":"10.1080/14728222.2024.2433124","url":null,"abstract":"Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease affecting the entire gastrointestinal tract with a progressive and relapsing course. Achieving mucosal healing has emerged as a critical therapeutic goal, as it is associated with sustained clinical remission, reduced hospitalizations, and fewer surgery rates. Therefore, targeting mucosal healing is essential for long-term control in CD.Areas covered: This review evaluates the efficacy of novel biologic therapies and small molecules in inducing mucosal healing, specifically targeting pathways like IL-12/23, IL-23, α4β7 integrins, Janus kinase 1 (JAK1), and sphingosine-1-phosphate receptor (S1PR) in adults (≥18 years) with moderate-to-severe CD. The rationale for selecting these specific pathways is their central role in modulating key inflammatory processes implicated in CD pathogenesis. We compare these therapies with placebo for both induction and maintenance of remission, based on a PubMed literature review for published articles and ClinicalTrials.gov for ongoing trials.Expert opinion: Upadacitinib and anti-IL23p19 agents (risankizumab, guselkumab and mirikizumab) are promising advanced non-TNF-targeting therapies for inducing endoscopic remission and mucosal healing but further studies are needed to integrate mucosal healing into a broader definition of endoscopic response, with a unified and precise definition.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"963-978"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring PKG signaling as a therapeutic avenue for pressure overload, ischemia, and HFpEF. 探索 PKG 信号转导作为压力过载、缺血和高房血症的治疗途径。

IF 5.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-01 Epub Date: 2024-09-27 DOI: 10.1080/14728222.2024.2400093

S Zhazykbayeva, H Budde, M Kaçmaz, Y Zemedie, H Osman, R Hassoun, K Jaquet, I Akin, I El-Battrawy, M Herwig, N Hamdani

{"title":"Exploring PKG signaling as a therapeutic avenue for pressure overload, ischemia, and HFpEF.","authors":"S Zhazykbayeva, H Budde, M Kaçmaz, Y Zemedie, H Osman, R Hassoun, K Jaquet, I Akin, I El-Battrawy, M Herwig, N Hamdani","doi":"10.1080/14728222.2024.2400093","DOIUrl":"10.1080/14728222.2024.2400093","url":null,"abstract":"Introduction: Heart failure (HF) is a complex and heterogeneous syndrome resulting from any diastolic or systolic dysfunction of the cardiac muscle. In addition to comorbid conditions, pressure overload, and myocardial ischemia are associated with cardiac remodeling which manifests as extracellular matrix (ECM) perturbations, impaired cellular responses, and subsequent ventricular dysfunction.Areas covered: The current review discusses the main aspects of the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway (cGMP-PKG) pathway modulators and highlights the promising outcomes of its novel pharmacological boosters.Expert opinion: Among several signaling pathways involved in the pathogenesis of pressure overload, ischemia and HF with preserved ejection fraction (HFpEF) is cGMP-PKG pathway. This pathway plays a pivotal role in the regulation of cardiac contractility, and modulation of cGMP-PKG signaling, contributing to the development of the diseases. Ventricular cardiomyocytes of HF patients and animal models are known to exhibit reduced cGMP levels and disturbed cGMP signaling including hypophosphorylation of PKG downstream targets. However, restoration of cGMP-PKG signaling improves cardiomyocyte function and promotes cardioprotective effects.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"857-873"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0